<i>In-silico</i> Evaluation of Novel Honokiol Derivatives against Breast Cancer Target Protein <i>LKB1</i>

Author(s):

Izzah Shahid*, Muhammad Shoaib, Rabail Zehra Raza, Muhammad Jahangir, Sumra Wajid Abbasi, Areej Riasat, Ansa Akbar and Samina Mehnaz   Pages 1388 - 1396 ( 9 )

Abstract:

<p>Background: Breast cancer is characterized by uncontrolled cell growth in the breast tissue and is a leading cause of death globally. Cytotoxic effects and reduced efficacy of currently used therapeutics insist to look for new chemo-preventive strategies against breast cancer. <i>LKB1</i> gene has recently been categorized as a tumor suppressor gene where its inactivation can cause sporadic carcinomas in various tissues. Mutations in the highly conserved <i>LKB1</i> catalytic domain lead to the loss of function and subsequently elevated expression of pluripotency factors in breast cancer. </p><p> Objective: The utilization of drug-likeness filters and molecular simulation has helped evaluate the pharmacological activity and binding abilities of selected drug candidates to the target proteins in many cancer studies. </p><p> Methods: The current<i> in silico</i> study provides a pharmacoinformatic approach to decipher the potential of novel honokiol derivatives as therapeutic agents against breast cancer. AutoDock Vina was used for molecular docking of the molecules. A 100 nano second (ns) molecular dynamics simulation of the lowest energy posture of 3&#039;-formylhonokiol- <i>LKB1</i>, resulting from docking studies, was carried out using the AMBER 18. </p><p> Results: Among the three honokiol derivatives, ligand-protein binding energy of 3&#039; formylhonokiol with <i>LKB1</i> protein was found to be the highest <i>via</i> molecular docking. Moreover, the stability and compactness inferred for 3&#039;- formylhonokiol with <i>LKB1</i> are suggestive of 3&#039; formylhonokiol being an effective activator of <i>LKB1</i> <i>via</i> simulation studies. </p><p> Conclusion: It was further established that 3&#039;- formylhonokiol displays an excellent profile of distribution, metabolism, and absorption, indicating it is an anticipated future drug candidate.</p>

Keywords:

Honokiol, breast cancer, molecular docking, virtual screening, <i>LKB1</i>,ADMET analysis.

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